Structural basis for engagement by complement factor H of C3b on a self surface
Open Access
- 31 March 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 18 (4), 463-U101
- https://doi.org/10.1038/nsmb.2018
Abstract
Complement factor H (FH) attenuates C3b molecules tethered by their thioester domains to self surfaces and thereby protects host tissues. Factor H is a cofactor for initial C3b proteolysis that ultimately yields a surface-attached fragment (C3d) corresponding to the thioester domain. We used NMR and X-ray crystallography to study the C3d-FH19-20 complex in atomic detail and identify glycosaminoglycan-binding residues in factor H module 20 of the C3d-FH19-20 complex. Mutagenesis justified the merging of the C3d-FH19-20 structure with an existing C3b-FH1-4 crystal structure. We concatenated the merged structure with the available FH6-8 crystal structure and new SAXS-derived FH1-4, FH8-15 and FH15-19 envelopes. The combined data are consistent with a bent-back factor H molecule that binds through its termini to two sites on one C3b molecule and simultaneously to adjacent polyanionic host-surface markers.Keywords
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